CHAPTER 34 OPIOID ANALGESICS Ronald Kanner, MD 1. Tolerance to the analgesic effects of opioids is well known. Does tolerance occur to the side effects, as well as the effects? Yes, tolerance occurs to the side effects, as well as the effects, but the rate of tolerance may be different. For example, pupillary constriction and constipation are chronic side effects that may continue as long as opioid dosing continues. However, tolerance to respiratory depression develops more rapidly. As opioid doses are increased to overcome analgesic tolerance, constipation and pupillary constriction persist, whereas respiratory depression may become less of a problem. 2. What is an opioid? “Opioid” is the term used to refer to a group of substances that have the analgesic and other properties of morphine. This includes the naturally occurring opiates, semisynthetic opiates, and endogenous opioids. The term “opiate” was initially used to denote any derivative of the poppy plant. As synthetic and semisynthetic products became available and endogenous peptides with morphinelike activity were identified, it became clear that the term had to be modified. It still holds some of its literary significance as any substance capable of assuaging suffering. 3. What is the role of opioids in pain management? Opioids have been the mainstay of treatment of moderate to severe pain in patients with cancer and in many acute pain syndromes. Although many patients with chronic noncancer pain have been successfully treated with opioids, their role in chronic pain of noncancer origin is still being defined. In the 1960s and 1970s, opioid treatment was considered the antithesis of good treatment for chronic pain of noncancer origin. In the 1980s and 1990s, it gained greater acceptance. For treatment of both cancer and noncancer chronic pain, there are few true long-term studies to help practitioners fully understand the potential benefits and risks of such therapy. In recent years, guidelines have been established for the safe and efficacious use of opioids in the treatment of many noncancer pain syndromes. The guidelines suggest that opioid therapy for chronic noncancer pain should be considered only after other reasonable attempts at analgesia have failed. A history of substance abuse or severe character pathology should be considered relative contraindications. One practitioner should manage the prescribed opiates, and he or she must be experienced in their use and able to recognize and deal with adverse reactions such as cognitive impairment, constipation, and aberrant use. The potential risks and benefits should be discussed with the patient and clearly documented in the patient file. New guidelines regarding the use of opioids in chronic noncancer pain are being developed as a collaborative effort among several major pain organizations and should be available soon. 4. What is a narcotic? Narcotic is now a term that has more legal implications than it does pharmacologic ones. It was initially used to denote any drug capable of producing sleep (narcosis). It was generally applied to the opiates. However, the term is now used to denote drugs of abuse that are controlled by government agencies. The old name for one of the federal agencies was the Bureau of Narcotics and Dangerous Drugs. Currently, the main regulatory agency on a national level is the Drug Enforcement Agency (DEA). The term opioid is now preferred instead of narcotic when describing opioid analgesics. 5. What are the two main, naturally occurring opioid alkaloids used in clinical practice? Morphine and codeine are two of the most widely used naturally occurring opioid alkaloids. Morphine is the prototype of the opioid drug. It binds primarily to mu receptors, producing analgesia and respiratory depression. 6. Describe the mechanism of opioid analgesia Opioid analgesia is thought to be mediated through a direct interaction with an opioid receptor. Thus far, the opioid receptors responsible for analgesia have been identified in the spinal cord, the brainstem, and the cerebral cortex. It is less clear at present what analgesic role is played by the opiate receptors that have been identified in the peripheral nervous system. 7. What is the difference between a “weak” and a “potent” analgesic? The weak analgesics have a ceiling effect. This implies that there is a dosing level after which side effects accrue more rapidly than analgesic effects. The potent opioids have no such ceiling. As tolerance develops or disease progresses, the doses can be increased. 8. Name some of the “weak” opioids and the problems associated with them Codeine is one of the most commonly used weak opioids. As doses escalate, nausea and constipation limit efficacy. For example, though 30 mg of codeine provides more analgesia than 15 mg, and 60 mg provides more than 30 mg, etc., higher doses are limited by side effects. Oxycodone is often listed as a weak opioid. However, this designation is mainly a function of the acetaminophen or aspirin with which it is commonly combined, and in reality, oxycodone by itself is likely more potent than morphine. When used as a single agent and not in combination with another agent, oxycodone can be given in increasing doses, without as clear a ceiling. 9. Name some “potent” opioids Morphine is the prototype of the potent group, against which other opioids have been judged despite the fact that other commonly prescribed drugs, including hydrocodone and oxycodone, are more potent than morphine. Morphine is a relatively short serum half-life drug (2 to 3 hours), as is hydromorphone. Methadone, another potent opioid, has a much longer terminal serum half-life, potentially extending to 54 hours; however, its analgesic serum half-life is often much shorter (6 to 8 hours, for example). Prescribing methadone in particular can be very challenging as a result because increasing the dose too quickly can lead to serious and potentially fatal outcomes. 10. What subtypes of opioid receptor are important in analgesia? The three main opioid subtypes are the mu, kappa, and delta receptors. From the standpoint of analgesia, the mu receptor seems to be the most important. There may be subtypes of these receptors, with different drugs having different affinities for given receptor subtypes and different patients having different receptor subtypes as well. There also may be analgesic activity at the delta and kappa sites. 11. Explain what is meant by a mixed agonist-antagonist drug When a drug combines with a receptor site and produces the action of that receptor, it is considered an agonist. A drug that binds with a receptor and inhibits activity is considered an antagonist. Naloxone is an example of a pure antagonist drug. Semisynthetic and synthetic products have been produced that are both agonist and antagonist at opioid receptors. The hope in producing these drugs was that they would be agonist for analgesic effects and antagonist for the respiratory depression and sedative effects of the opioids. Examples of mixed agonist-antagonist drugs include pentazocine, butorphanol, and buprenorphine. New preparations of these drugs, specifically buprenorphine, are being or have been developed. In fact, the administration of a mixed agonist-antagonist drug to a patient who is physically dependent on an agonist may produce a withdrawal syndrome. 12. What are the endogenous opioids? The first endogenous opioids to be discovered were the endorphins and enkephalins. These are polypeptides that are synthesized in the brain and spinal cord. They bind with opioid receptors and produce analgesia. Since the discovery of endorphins and enkephalins in the early 1970s, a number of other peptide products have been described. 13. How do mixed agonist-antagonist drugs differ from pure agonist analgesics? Clinically, the most important concept is that these mixed drugs have a ceiling effect. That is, with increasing doses, side effects supervene, and further analgesia cannot be achieved. When tolerance develops to pure agonist drugs, drug doses can be increased to obtain further analgesia. In patients who are opioid dependent, administration of a mixed agonist-antagonist may precipitate withdrawal. 14. Differentiate efficacy and potency Efficacy refers to the ability of the drug to produce a given response in an appropriate clinical setting. Potency refers either to the number of milligrams required to produce an effect or to the affinity with which a drug binds to a receptor. Thus a drug may be very potent (able to produce a response at a very low dose) but not have great efficacy (because of intolerable side effects). 15. Only gold members can continue reading. Log In or Register to continue Share this:Click to share on Twitter (Opens in new window)Click to share on Facebook (Opens in new window) Related Related posts: Neuroimaging in the Patient with Pain Pharmacologic Management Postoperative Pain Management Sympathetic Neural Blockade Cancer Pain Syndromes Temporary Neural Blockade Stay updated, free articles. Join our Telegram channel Join Tags: Pain Management Secrets Jun 14, 2016 | Posted by admin in PAIN MEDICINE | Comments Off on Opioid Analgesics Full access? Get Clinical Tree
CHAPTER 34 OPIOID ANALGESICS Ronald Kanner, MD 1. Tolerance to the analgesic effects of opioids is well known. Does tolerance occur to the side effects, as well as the effects? Yes, tolerance occurs to the side effects, as well as the effects, but the rate of tolerance may be different. For example, pupillary constriction and constipation are chronic side effects that may continue as long as opioid dosing continues. However, tolerance to respiratory depression develops more rapidly. As opioid doses are increased to overcome analgesic tolerance, constipation and pupillary constriction persist, whereas respiratory depression may become less of a problem. 2. What is an opioid? “Opioid” is the term used to refer to a group of substances that have the analgesic and other properties of morphine. This includes the naturally occurring opiates, semisynthetic opiates, and endogenous opioids. The term “opiate” was initially used to denote any derivative of the poppy plant. As synthetic and semisynthetic products became available and endogenous peptides with morphinelike activity were identified, it became clear that the term had to be modified. It still holds some of its literary significance as any substance capable of assuaging suffering. 3. What is the role of opioids in pain management? Opioids have been the mainstay of treatment of moderate to severe pain in patients with cancer and in many acute pain syndromes. Although many patients with chronic noncancer pain have been successfully treated with opioids, their role in chronic pain of noncancer origin is still being defined. In the 1960s and 1970s, opioid treatment was considered the antithesis of good treatment for chronic pain of noncancer origin. In the 1980s and 1990s, it gained greater acceptance. For treatment of both cancer and noncancer chronic pain, there are few true long-term studies to help practitioners fully understand the potential benefits and risks of such therapy. In recent years, guidelines have been established for the safe and efficacious use of opioids in the treatment of many noncancer pain syndromes. The guidelines suggest that opioid therapy for chronic noncancer pain should be considered only after other reasonable attempts at analgesia have failed. A history of substance abuse or severe character pathology should be considered relative contraindications. One practitioner should manage the prescribed opiates, and he or she must be experienced in their use and able to recognize and deal with adverse reactions such as cognitive impairment, constipation, and aberrant use. The potential risks and benefits should be discussed with the patient and clearly documented in the patient file. New guidelines regarding the use of opioids in chronic noncancer pain are being developed as a collaborative effort among several major pain organizations and should be available soon. 4. What is a narcotic? Narcotic is now a term that has more legal implications than it does pharmacologic ones. It was initially used to denote any drug capable of producing sleep (narcosis). It was generally applied to the opiates. However, the term is now used to denote drugs of abuse that are controlled by government agencies. The old name for one of the federal agencies was the Bureau of Narcotics and Dangerous Drugs. Currently, the main regulatory agency on a national level is the Drug Enforcement Agency (DEA). The term opioid is now preferred instead of narcotic when describing opioid analgesics. 5. What are the two main, naturally occurring opioid alkaloids used in clinical practice? Morphine and codeine are two of the most widely used naturally occurring opioid alkaloids. Morphine is the prototype of the opioid drug. It binds primarily to mu receptors, producing analgesia and respiratory depression. 6. Describe the mechanism of opioid analgesia Opioid analgesia is thought to be mediated through a direct interaction with an opioid receptor. Thus far, the opioid receptors responsible for analgesia have been identified in the spinal cord, the brainstem, and the cerebral cortex. It is less clear at present what analgesic role is played by the opiate receptors that have been identified in the peripheral nervous system. 7. What is the difference between a “weak” and a “potent” analgesic? The weak analgesics have a ceiling effect. This implies that there is a dosing level after which side effects accrue more rapidly than analgesic effects. The potent opioids have no such ceiling. As tolerance develops or disease progresses, the doses can be increased. 8. Name some of the “weak” opioids and the problems associated with them Codeine is one of the most commonly used weak opioids. As doses escalate, nausea and constipation limit efficacy. For example, though 30 mg of codeine provides more analgesia than 15 mg, and 60 mg provides more than 30 mg, etc., higher doses are limited by side effects. Oxycodone is often listed as a weak opioid. However, this designation is mainly a function of the acetaminophen or aspirin with which it is commonly combined, and in reality, oxycodone by itself is likely more potent than morphine. When used as a single agent and not in combination with another agent, oxycodone can be given in increasing doses, without as clear a ceiling. 9. Name some “potent” opioids Morphine is the prototype of the potent group, against which other opioids have been judged despite the fact that other commonly prescribed drugs, including hydrocodone and oxycodone, are more potent than morphine. Morphine is a relatively short serum half-life drug (2 to 3 hours), as is hydromorphone. Methadone, another potent opioid, has a much longer terminal serum half-life, potentially extending to 54 hours; however, its analgesic serum half-life is often much shorter (6 to 8 hours, for example). Prescribing methadone in particular can be very challenging as a result because increasing the dose too quickly can lead to serious and potentially fatal outcomes. 10. What subtypes of opioid receptor are important in analgesia? The three main opioid subtypes are the mu, kappa, and delta receptors. From the standpoint of analgesia, the mu receptor seems to be the most important. There may be subtypes of these receptors, with different drugs having different affinities for given receptor subtypes and different patients having different receptor subtypes as well. There also may be analgesic activity at the delta and kappa sites. 11. Explain what is meant by a mixed agonist-antagonist drug When a drug combines with a receptor site and produces the action of that receptor, it is considered an agonist. A drug that binds with a receptor and inhibits activity is considered an antagonist. Naloxone is an example of a pure antagonist drug. Semisynthetic and synthetic products have been produced that are both agonist and antagonist at opioid receptors. The hope in producing these drugs was that they would be agonist for analgesic effects and antagonist for the respiratory depression and sedative effects of the opioids. Examples of mixed agonist-antagonist drugs include pentazocine, butorphanol, and buprenorphine. New preparations of these drugs, specifically buprenorphine, are being or have been developed. In fact, the administration of a mixed agonist-antagonist drug to a patient who is physically dependent on an agonist may produce a withdrawal syndrome. 12. What are the endogenous opioids? The first endogenous opioids to be discovered were the endorphins and enkephalins. These are polypeptides that are synthesized in the brain and spinal cord. They bind with opioid receptors and produce analgesia. Since the discovery of endorphins and enkephalins in the early 1970s, a number of other peptide products have been described. 13. How do mixed agonist-antagonist drugs differ from pure agonist analgesics? Clinically, the most important concept is that these mixed drugs have a ceiling effect. That is, with increasing doses, side effects supervene, and further analgesia cannot be achieved. When tolerance develops to pure agonist drugs, drug doses can be increased to obtain further analgesia. In patients who are opioid dependent, administration of a mixed agonist-antagonist may precipitate withdrawal. 14. Differentiate efficacy and potency Efficacy refers to the ability of the drug to produce a given response in an appropriate clinical setting. Potency refers either to the number of milligrams required to produce an effect or to the affinity with which a drug binds to a receptor. Thus a drug may be very potent (able to produce a response at a very low dose) but not have great efficacy (because of intolerable side effects). 15. Only gold members can continue reading. Log In or Register to continue Share this:Click to share on Twitter (Opens in new window)Click to share on Facebook (Opens in new window) Related Related posts: Neuroimaging in the Patient with Pain Pharmacologic Management Postoperative Pain Management Sympathetic Neural Blockade Cancer Pain Syndromes Temporary Neural Blockade Stay updated, free articles. Join our Telegram channel Join Tags: Pain Management Secrets Jun 14, 2016 | Posted by admin in PAIN MEDICINE | Comments Off on Opioid Analgesics Full access? Get Clinical Tree
